During the blood clotting mechanism, platelets rapidly respond to form a thrombus in cooperation with fibrinogen. At the site of injury, platelets bind to fibrinogen which initiates platelet aggregation to form the thrombus. As currently understood, a significant aspect of the aggregation process involves Glycoprotein(gp)IIb/IIIa, a platelet surface integrin which binds fibrinogen and links together activated platelets to form an aggregate.
Deep vein thrombosis (DVT) and pulmonary embolism (PE) are common clinical observations resulting from thrombus formation and are associated with nearly 5 million patients in the United States alone. PE results in over 100,000 deaths per year and patients with DVT formation have a high probablity of PE formation. Several interventional methods using an anticoagulant or fibrinolytic have been utilized to treat DVT and PE, including treatment with heparin, streptokinase or recombinant tissue plasminogen activators. Before these treatments can begin, however, the diagnosis of the condition must be made.
Diagnostic radionuclides have been successfully used to detect various pathological conditions. The method is effective when the radionuclide can be effectively attached to a moiety that can localize to a selected biological site without interfering with the localization or binding of the localizing moiety. In this manner, the rapid identification of these sites becomes possible.
Various approaches for the detection of thrombi have been proposed. Existing non-radionuclide based methods of detecting and diagnosing thrombus formation include contrast venography and ultrasound. A prior knowledge of thrombus formation is highly desirable for either of these methods to be used advantageously and the venography technique is invasive. Radiolabeled thrombin inhibitors, plasmin, plasminogen activators such as TPA, heparin, fibronectin and anti-platelet monoclonal antibodies have also variously been proposed and used to radioimage thrombi. These radiolabelled approaches, however, present numerous disadvantages which limit their desirability as a diagnostic radiopharmaceutical. Most significantly, a long waiting period between injection and imaging is typically associated with these radiolabelled compositions which is considered undesirable in terms of patient comfort and ease of use.
Hence, a need exists for a diagnostic composition that rapidly locates sites of thrombus in vivo to facilitate a determination as to whether further diagnostic and/or therapeutic treatment is necessary or to provide a quick and reliable means to follow the course of prior treatment of a thrombus.